The activity of the C4-dicarboxylic acid chemoreceptor of Pseudomonas aeruginosa is controlled by chemoattractants and antagonists
Chemotaxis toward organic acids has been associated with colonization fitness and virulence and the opportunistic pathogen Pseudomonas aeruginosa exhibits taxis toward several tricarboxylic acid intermediates. In this study, we used high-throughput ligand screening and isothermal titration calorimet...
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Veröffentlicht in: | Scientific reports 2018-02, Vol.8 (1), p.2102-12, Article 2102 |
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Zusammenfassung: | Chemotaxis toward organic acids has been associated with colonization fitness and virulence and the opportunistic pathogen
Pseudomonas aeruginosa
exhibits taxis toward several tricarboxylic acid intermediates. In this study, we used high-throughput ligand screening and isothermal titration calorimetry to demonstrate that the ligand binding domain (LBD) of the chemoreceptor PA2652 directly recognizes five C4-dicarboxylic acids with
K
D
values ranging from 23 µM to 1.24 mM.
In vivo
experimentation showed that three of the identified ligands act as chemoattractants whereas two of them behave as antagonists by inhibiting the downstream chemotaxis signalling cascade.
In vitro
and
in vivo
competition assays showed that antagonists compete with chemoattractants for binding to PA2652-LBD, thereby decreasing the affinity for chemoattractants and the subsequent chemotactic response. Two chemosensory pathways encoded in the genome of
P. aeruginosa
,
che
and
che2
, have been associated to chemotaxis but we found that only the
che
pathway is involved in PA2652-mediated taxis. The receptor PA2652 is predicted to contain a sCACHE LBD and analytical ultracentrifugation analyses showed that PA2652-LBD is dimeric in the presence and the absence of ligands. Our results indicate the feasibility of using antagonists to interfere specifically with chemotaxis, which may be an alternative strategy to fight bacterial pathogens. |
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ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-018-20283-7 |